Mutations in codon 12, 13, or 61 convert H-ras, K-ras, and N-ras into oncogenes. Such mutationally activated Ras proteins are found in about 30% of human tumors. Despite their medical importance, specific therapeutic agents directly targeting Ras proteins have not yet been discovered. To develop such Ras inhibitors, we have identified peptide aptamers that interact with oncogenic RasV12 from human tumors. Furthermore, we have demonstrated that these peptide aptamers inhibit the Ras/Raf signal transduction pathway in mammalian cells. Moreover, we have shown that these Ras peptide aptamers inhibit tumor growth in vitro and in mice bearing human tumor xenografts. Here, we propose to further characterize: 1. Peptide aptamers that inhibit Ras functions. 2. Peptide aptamers that interact with oncogenic Ras. 3. Peptide aptamers that inhibit tumorigenesis. These studies provide a new systematic framework for developing inhibitors of any proteins of biological and/or medical importance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA108795-03
Application #
7256365
Study Section
Drug Discovery and Molecular Pharmacology Study Section (DMP)
Program Officer
Forry, Suzanne L
Project Start
2005-07-01
Project End
2008-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$320,225
Indirect Cost
Name
Biological Research Institute
Department
Type
DUNS #
168990229
City
Pasadena
State
CA
Country
United States
Zip Code
91101
Yamazaki, Hiroto; Xu, C Wilson; Naito, Motohiko et al. (2011) Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia. Biochem Biophys Res Commun 409:14-21